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Flashcards in Animal Models Deck (16)
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1

Classical models of Parkinson's

Toxic models:
- MPTP (mice, primates)
- 6-hydroxydopamine (rats, mice)
- paraquat (rats, mice)
- rotenone (rats)

2

PD sporadic vs familial

90% - sporadic
- environment
- possibly genetic factors
10% - familial
- mutations

3

Symptoms of PD

Akinesia
Postural imbalance
Rigidity
Olfactory loss
Tremor
Cognitive disorders (implicit memory)
Affective disorders (depression / anxiety / apathy)
Sleep disturbances
Autonomic disorders (hypotension)
Digestive symptoms (constipation)

Other Symptoms:
- Constipation (Lewy bodies found in the neurons of the intestinal wall)
- Various neurons with long axons show Lewy bodies before the dopaminergic ones
- Sleep disorders
- Depression
- psychosis
- Anosmia

- Mask face
- Micrographia
- Hypersalivation

4

Allocation concealment

Concealing the allocation sequence from those assigning animals to intervention groups, until the moment of assignment.

5

Bias

Systematic distortion of the estimated intervention effect away from the “truth,” caused by inadequacies in the design, conduct, or analysis of an experiment.

6

Blinding (masking)

Keeping the persons who perform the experiment, collect data, and assess outcome unaware of the treatment allocation

7

External validity

The extent to which the results of an animal experiment provide a correct basis for generalisations to the human condition.

8

Intention-to-treat analysis

Analysis of data of all animals included in the group to which they were assigned, regardless of whether they completed the intervention.

9

Internal validity

The extent to which the design and conduct of the trial eliminate the possibility of bias.

10

Biases threatening internal validity:

- selection bias (biased allocation to treatment groups) [sol.: randomization, allocation concealment]
- performance bias (systematic differences in care between groups apart from the intervention) [sol.: blinding]
- detection (ascertainment, assessment, or observer bias: systematic distortion of the results of a study that occurs when the person assessing the outcome has knowledge of treatment assignment) [sol.; blinding]
- attrition bias (unequal occurrence and handling of deviations from protocols and loss to follow-up between treatment groups) [sol:blinding, intention-to-treat, reporting drop outs]
- false positive report bias (bias due to poor statistical power) [sol: adequate sample size]

11

Common problems with external validity:

- Induction of one disease in animals that are young and healthy, whereas in patients the disease mainly occurs in elderly people with co-morbidities.
- Assessment of the effect of a treatment in a homogeneous group of animals versus a heterogeneous group of patients.
- The use of either male or female animals, whereas the disease occurs in male and female patients.
- use of models for inducing a disease or injury with insufficient similarity to the human condition.
- Unrealistic timing and dosage of treatment in animals vs human.
- Differences in outcome measures and the timing of outcome assessment between animal studies and clinical trials.

12

Aspects of a study to be reported:

- sample size calculation
- eligibility criteria
- treatment allocation (If this allocation was by randomisation, the method of randomisation)
- allocation concealment
- blinding
- flow of animals (Flow of animals through each stage of the study, with a specific attention to animals excluded from the analyses. Reasons for exclusion from the analyses.)
- control of physiological variables
- control of study conduct (Whether a third party controlled which parts of the conduct of the study.)
- statistical

13

Stages for describing seizure behavior:

Racine 1972
- I freeze / mild facial clonus
- II severe facial clonus
- III forelimb clonus
- IV rearing
- V falling
Fully Kindled = 5 * stage V

14

EEG readout info in epilepsy

- latency - time between hit and
- epileptic spikes
- seizure duration
- spike frequency

15

Side effects of VNS:

- bradycardia and decreased respiration rate (at stronger current)
- SO2 96% to 86%
- coughing
- immobility
- Horner’s syndrome
- vocalizing
-grooming
- polyuria
- trears
- headturn
- >defecation frequency
- drooling swallow

16

Features of VNS that define its efficiency

- electrode design, ?
- electrode is (not) around the carotid artery, ?
- stimulation parameters
- anesthesia no/yes, how?
- responder definition